CAREER: Modeling and Decoding Host-Microbiome Interactions in Gingival Tissue

职业：建模和解码牙龈组织中宿主-微生物组的相互作用

• 批准号: 2337322
• 负责人: Chiara Ghezzi
• 金额: $ 64.94万
• 依托单位: University of Massachusetts Lowell
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-06-01 至 2029-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2337322&HistoricalAwards=false
• 关键词: CAREER; Modeling; Decoding; Host; Microbiome

The human body houses many different, but connected, microbial populations. For example, populations of tiny living things like bacteria, viruses and fungi, that can’t be seen with the naked eye. Some microbes make us sick while others are important for our health. Their balance or imbalance with each other and the surrounding tissues can exert long-lasting and wide-ranging effects on an individual’s state of health or disease. Of particular interest is the microbiota in the oral cavity, as it serves as a potential reservoir for pathogenic (disease causing) bacteria. However, very little is known about the relationship of various diseases and the oral microbiome. The research goal of this CAREER project is to understand the connection between the human oral tissue, the oral microbiome, and how they interact. This will be accomplished by creating an in vitro (in the lab) model of the human gingival (gum) tissue system capable of studying diverse microbial populations and their connection to overall human health. The goal of the project’s educational plan, called ResAx, is to provide a working model to address the drop in enrollment in low resources academic institutions that could be transposed to other research areas (i.e., medical devices, protein engineering). The multidisciplinary research project will provide opportunities to expand research access and education to undergraduate students enrolled in the BME curriculum at University of Massachusetts Lowell and to support a paid Summer Training Program for rising junior high school students in the local Lowell community. ResAx aims to provide equitable access to high-quality education experiences to more than 5,000 underserved students.This CAREER project targets the development of an in vitro gingival tissue system to study the role of microbial communities on human oral health and disease, with potential repercussion on diverse pathologies such as periodontitis, atopic dermatitis, asthma, and inflammatory bowel disease. In addition to representing a large population and economic market, these chronic diseases are emergent drivers of global socioeconomic status. The vision of this CAREER project will be accomplished by: (i) the development and validation of a microphysiological system to study oral host-pathogens interactions and microbiome biogeography under different clinical conditions (healthy, gingivitis and periodontitis); (ii) the engineering of an inflamed gingivitis model based on human primary neutrophils to identify a clinical fingerprint for early dysbiosis presentation; and (iii) a periodontitis model based on activated B and T lymphocytes and clinically driven tissue characteristics to investigate the effect of lipid mediators on inflammation resolution and induced changes on the established polymicrobial community.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

人体容纳许多不同但相关的微生物种群。例如，细菌，病毒和真菌等微小的生物种群无法用肉眼看到。一些微生物使我们生病，而另一些则对我们的健康很重要。他们彼此之间的平衡或失衡，周围的组织会对个人的健康或疾病状态产生持久和宽范围的影响。特别令人感兴趣的是口腔中的微生物群，因为它是病原（疾病引起的）细菌的潜在研究。但是，对于各种疾病和口腔微生物组的关系知之甚少。该职业项目的研究目标是了解人口腔组织，口腔微生物组以及它们如何相互作用之间的联系。这将通过创建人类牙龈（GUM）组织系统的体外（实验室）模型来实现，该模型能够研究潜水微生物种群及其与整体人类健康的联系。该项目的教育计划（称为RESAX）的目标是提供一个工作模型，以解决低资源学术机构入学率下降，这些学术机构可以转化为其他研究领域（即医疗设备，蛋白质工程）。多学科研究项目将为洛厄尔大学（University of Massachusetts Lowell）的BME课程招生的本科生提供扩大研究访问和教育的机会，并为当地洛厄尔社区中崛起的初中学生提供带薪夏季培训计划。 RESAX旨在为5,000多名服务不足的学生提供公平的高质量教育经验。该职业项目的目标是开发体外牙龈组织系统，以研究微生物群落在人类口腔健康和疾病中的作用，并潜在地反映了潜在的反应对潜在的病理学，例如牙周炎，牙周炎，炎症性皮肤炎，ASTHMA，ASTHMA，ASTHMA，ASTHMA，ASTHMA，ASTHMA，ASTHMA，疾病。除了代表大量人口和经济市场外，这些慢性疾病是全球社会经济地位的紧急驱动因素。该职业项目的愿景将通过：（i）在不同的临床状况（健康，牙龈炎和牙周炎）下研究口服宿主关系相互作用和微生物组生物地理学的微生物生理系统的开发和验证； （ii）基于人类原发性嗜中性粒细胞的发炎牙龈炎模型的工程，以鉴定早期营养不良症状的临床指纹； and (iii) a periodontitis model based on activated B and T lymphocytes and clinically driven tissue characteristics to investigate the effect of lipid mediators on inflammation resolution and induced changes on the established polymicrobial community.This award reflects NSF's statutory mission and has been Deemed honestly of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.